REDUCED EXPRESSION OF C-FOS IN FEMALE NOD MOUSE THYMOCYTES AND UP-REGULATION WITH HUMAN LYMPHOTOXIN

Previously we reported that the administration of human (h) lymphotoxi n (h-LT) markedly protected NOD mice from insulin dependent diabetes m ellitus (IDDM) partly by affecting the generation phase of anti-islet effector cells, probably in the thymus. In this study, we investigated the effect of h-LT on the signal transduction of the mouse thymocytes by observing c-Fos expression in the thymocytes by using a flow cytom eter, The intensity of c-Fos expression in whole thymocytes was signif icantly lower in the female NOD with a high incidence of diabetes than that in the male NOD mice with a low incidence of diabetes and than t hat in normal mice (P < 0.0001), The low c-Fos expression in the femal e NOD thymocytes was most prominent in CD3(low) thymocytes, c-Jun expr ession of the CD3(low) thymocytes was also lower in the female NOD mic e. Administrations of h-LT, h-TNF, and h-IL-2, which has been reported to prevent IDDM in NOD mice by systemic administration, significantly up-regulated c-Fos expression in CD3(low) thymocytes, From these resu lts, it is assumed that a relationship may exist between the high diab etes incidence and the defective c-Fos expression in female NOD mice a nd between the prevention of IDDM and the amelioration of the defectiv e c-Fos expression with h-LT in female NOD mice. (C) 1995 Academic Pre ss, Inc.